Histiocytoses

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9 regimens on this page
10 variants on this page


Erdheim-Chester disease (ECD)

Sirolimus & Prednisone

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Regimen

Study Evidence
Gianfreda et al. 2015 Pilot, <20 pts in this arm

Chemotherapy

  • Sirolimus (Rapamune) 2 mg PO once per day, titrated to achieve a blood level of 8 to 12 ng/mL
  • Prednisone (Sterapred) as follows:
    • Month 1: 0.75 mg/kg/day PO
    • Month 2: 0.5 mg/k/day PO
    • Months 3 & 4: 0.25 mg/kg/day PO
    • Months 5 & 6: 0.125 mg/kg/day PO
    • Month 7 onwards: tapered to a dose of 2.5 to 5 mg PO once per day

Given for up to 2 years for responders and stable disease, with optional extension beyond 2 years

References

  1. Gianfreda D, Nicastro M, Galetti M, Alberici F, Corradi D, Becchi G, Baldari G, De Filippo M, Ferretti S, Moroni G, Foti R, Di Gangi M, Jeannin G, Saffroy R, Emile JF, Buzio C, Vaglio A. Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial. Blood. 2015 Sep 3;126(10):1163-71. Epub 2015 Jun 3. link to original article contains verified protocol PubMed

Vemurafenib (Zelboraf)

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Regimen #1

Study Evidence
Hyman et al. 2015 Phase II, <20 pts in this arm

This was part of a basket trial, all patients had BRAF V600E mutations.

Chemotherapy

Duration of treatment not specified

Regimen #2

Study Evidence
Haroche et al. 2014 Pilot, <20 pts

Patients enrolled all had BRAF V600E mutation. This is the dose after de-escalation after the first four patients had excess adverse events.

Chemotherapy

Given until progression of disease or unacceptable toxicity

References

  1. Haroche J, Cohen-Aubart F, Emile JF, Maksud P, Drier A, Tolédano D, Barete S, Charlotte F, Cluzel P, Donadieu J, Benameur N, Grenier PA, Besnard S, Ory JP, Lifermann F, Idbaih A, Granel B, Graffin B, Hervier B, Arnaud L, Amoura Z. Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With BRAFV600E-Mutated Erdheim-Chester Disease. J Clin Oncol. 2015 Feb 10;33(5):411-8. Epub 2014 Nov 24. link to original article contains verified protocol PubMed
  2. Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015 Aug 20;373(8):726-736. link to original article contains protocol PubMed

Langerhans cell histiocytosis (LCH)

Cladribine (Leustatin)

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Regimen

Study Evidence
Weitzman et al. 2009 (LCH-S-98) Phase II

To be completed

Chemotherapy

References

  1. Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Pötschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH). results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. link to original article PubMed

Cladribine & Cytarabine

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Regimen

Study Evidence
Donadieu et al. 2015 Phase II

Chemotherapy, induction

  • Cladribine (Leustatin) 9 mg/m2 IV over 2 hours once per day on days 2 to 6, should not be administered simultaneously with cytarabine
    • Children weighing less than 10 kg received a dose of 0.3 mg/kg/day
  • Cytarabine (Cytosar) 500 mg/m2 IV over 2 hours twice per day on days 1 to 5, should not be administered simultaneously with cladribine

5-week cycle for 2 or more cycles

Patients with a "good response" proceeded to consolidation therapy:

Chemotherapy, consolidation

21-day cycle for 2 cycles, followed by:

Chemotherapy, maintenance

Total of 18 months of maintenance

References

  1. Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. link to original article contains verified protocol PubMed

Etoposide & Prednisone

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Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2001 (LCH-I) Phase III Vinblastine & Prednisone Seems not superior

To be completed

Chemotherapy

References

  1. Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. link to original article PubMed

Etoposide, Vinblastine, Prednisone

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Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2007 (LCH-II) Phase III Vinblastine & Prednisone Seems not superior

Total duration of therapy is 24 weeks.

Chemotherapy, initial

6-week course, followed by:

Chemotherapy, continuation

3-week cycle for 6 cycles

References

  1. Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. link to original article contains verified protocol PubMed

Methotrexate, Vinblastine, Prednisone

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Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2013 (LCH-III) Phase III Vinblastine & Prednisone Seems not superior

To be completed

Chemotherapy

References

  1. Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. link to original article PubMed

Vemurafenib (Zelboraf)

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Regimen

Study Evidence
Hyman et al. 2015 Phase II, <20 pts in this arm

This was part of a basket trial, all patients had BRAF V600E mutations.

Chemotherapy

Duration of treatment not specified

References

  1. Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015 Aug 20;373(8):726-736. link to original article contains protocol PubMed

Vinblastine & Prednisone

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Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2001 (LCH-I) Phase III Etoposide & Prednisone Seems not superior
Gadner et al. 2007 (LCH-II) Phase III Etoposide, Vinblastine, Prednisone Seems not superior
Gadner et al. 2013 (LCH-III) Phase III Methotrexate, Vinblastine, Prednisone Seems not superior

Total duration of therapy is 24 weeks, in LCH-II.

Chemotherapy, initial

6-week course, followed by:

Chemotherapy, continuation

3-week cycle for 6 cycles

References

  1. Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. link to original article PubMed
  2. Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. link to original article contains verified protocol PubMed
  3. Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. link to original article PubMed